WO2016061754A1 - 一种手持式分子影像导航系统 - Google Patents

一种手持式分子影像导航系统 Download PDF

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WO2016061754A1
WO2016061754A1 PCT/CN2014/089150 CN2014089150W WO2016061754A1 WO 2016061754 A1 WO2016061754 A1 WO 2016061754A1 CN 2014089150 W CN2014089150 W CN 2014089150W WO 2016061754 A1 WO2016061754 A1 WO 2016061754A1
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image
visible light
module
time division
spectral
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PCT/CN2014/089150
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English (en)
French (fr)
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田捷
迟崇巍
杨鑫
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中国科学院自动化研究所
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Priority to US15/520,928 priority Critical patent/US10524665B2/en
Priority to PCT/CN2014/089150 priority patent/WO2016061754A1/zh
Publication of WO2016061754A1 publication Critical patent/WO2016061754A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N23/00—Cameras or camera modules comprising electronic image sensors; Control thereof
    • H04N23/56—Cameras or camera modules comprising electronic image sensors; Control thereof provided with illuminating means
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2560/00—Constructional details of operational features of apparatus; Accessories for medical measuring apparatus
    • A61B2560/04—Constructional details of apparatus
    • A61B2560/0431—Portable apparatus, e.g. comprising a handle or case
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2576/00—Medical imaging apparatus involving image processing or analysis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0033—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room
    • A61B5/0035—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room adapted for acquisition of images from more than one imaging mode, e.g. combining MRI and optical tomography
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0077—Devices for viewing the surface of the body, e.g. camera, magnifying lens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/72—Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7235—Details of waveform analysis
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H30/00—ICT specially adapted for the handling or processing of medical images
    • G16H30/40—ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N23/00—Cameras or camera modules comprising electronic image sensors; Control thereof
    • H04N23/10—Cameras or camera modules comprising electronic image sensors; Control thereof for generating image signals from different wavelengths
    • H04N23/11—Cameras or camera modules comprising electronic image sensors; Control thereof for generating image signals from different wavelengths for generating image signals from visible and infrared light wavelengths
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N5/00—Details of television systems
    • H04N5/222—Studio circuitry; Studio devices; Studio equipment
    • H04N5/262—Studio circuits, e.g. for mixing, switching-over, change of character of image, other special effects ; Cameras specially adapted for the electronic generation of special effects
    • H04N5/265—Mixing

Definitions

  • the invention relates to an imaging system, in particular to a hand-held molecular image navigation system.
  • molecular imaging essentially reflects changes in the level of physiological molecules of organisms and changes in overall function caused by changes in molecular regulation. Therefore, studying the life activities of genes, biomacromolecules and cells in vivo at the molecular level is an important technology, including in vivo bio-optics based on molecular techniques, tomography, optical imaging techniques, and simulation methods.
  • the basic research of imaging technology has become one of the hotspots and difficulties in the field of molecular imaging research.
  • Molecular imaging equipment combines traditional medical imaging technology with modern molecular biology to observe physiological or pathological changes at the cellular and molecular levels. It has the advantages of non-invasive, real-time, in vivo, high specificity, high sensitivity and high resolution imaging. .
  • the use of molecular imaging technology can speed up the development of drugs, shorten the pre-clinical research time of drugs, and provide more accurate diagnosis, so that the treatment plan can best match the patient's genetic map.
  • it can be applied in the field of biomedicine to achieve targets such as quantitative analysis, image navigation, and molecular typing in vivo.
  • the system using this method is relatively complicated, and the ease of operation and the comfort of use need to be further improved.
  • the present invention proposes a hand-held molecular image navigation system, which enhances the application range of the application by real-time imaging of fluorescence and visible light of different spectra by time-sharing control method.
  • Embodiments of the present invention provide a handheld molecular image navigation system, including:
  • a multi-spectral light source module configured to provide a plurality of different spectral segments of light in a time division control manner according to a control signal sequence to illuminate the object to be inspected;
  • a time division control module configured to generate the control signal sequence
  • An optical signal acquisition module configured to acquire a near-infrared fluorescence image and a visible light image of the object to be inspected according to a control signal sequence provided by the time division control module in a time division control manner;
  • a processing module configured to acquire the near-infrared fluorescent image and the visible light image according to the control signal sequence
  • For image processing fusion of the visible light image and the fluorescent image is performed and the fused image is output, and the feedback signal is output according to the collected near-infrared fluorescence image and the visible light image to optimize the control signal sequence.
  • the handheld molecular imaging system further comprises a handheld system housing module for housing the multi-spectral light source module, the time division control module and the signal acquisition module.
  • the multi-spectral light source module comprises:
  • a background light source for providing visible light
  • a near-infrared source for providing near-infrared light
  • a first multi-spectral switch for controlling the background light source and the near-infrared light source to be alternately turned on and off according to a time division control signal sequence from the time division control module, thereby illuminating the visible light when the optical signal acquisition module collects the fluorescent image, and when collecting The near-infrared light is illuminated when the visible light background image.
  • the optical signal acquisition module comprises:
  • a camera for collecting near-infrared fluorescence images and visible light images of the subject
  • a second multi-spectral switch disposed at a front end of the camera
  • the timing signal controller is configured to receive the control signal sequence from the time division control module, and control the switching of the second multi-spectral switch according to the received control signal sequence, so that the camera performs the collection of the corresponding visible light image and the fluorescent image.
  • the time division control module comprises:
  • timing signal generator for generating a control signal according to different optical signal sources
  • a signal controller for converting a control signal from the timing signal generator into a sequence of control signals having a system usable format to control operation of the first spectral switcher and the second spectral switcher.
  • the processing module comprises:
  • timing control feedback module configured to monitor a sequence of control signals output by the time division control module according to the collected visible light image and the fluorescence image, to determine whether adjustment of the operation of the first multispectral switch and/or the second multispectral switch is required, And returning a feedback signal to the signal controller based on the determination result;
  • the image processing module is configured to perform image processing on the collected visible light image and the fluorescent image in each time interval, and fuse the processed visible light image with the processed near-infrared fluorescent image, and output the fused image.
  • multi-spectral real-time imaging is realized by image acquisition and processing.
  • the multi-spectral switcher and the time-division control module are used together with the timing control, so that the molecular image navigation can be effectively realized, the detection light intensity is maximized, and useful information is effectively retained.
  • the strong fluorescence information be seen, but also the observer can see the information of the visible light, and the light of the two spectra does not affect each other.
  • FIG. 1 is a schematic diagram showing the appearance of a handheld system housing module according to an embodiment of the present invention
  • FIG. 2 shows a block diagram of a handheld molecular image navigation system in accordance with an embodiment of the present invention
  • FIG. 3 is a timing diagram showing the control of the time division control module of FIG.
  • Embodiments of the present invention provide a handheld molecular imaging navigation system based on excitation fluorescence imaging in molecular imaging.
  • the handheld molecular image navigation system may include a multi-spectral light source module 110 for providing light of a plurality of different spectral segments in a time division control manner to illuminate a subject; the time division control module 130 for generating a control signal sequence; an optical signal acquisition module 120, configured to acquire a near-infrared fluorescence image and a visible light image of the object to be inspected according to a control signal sequence provided by the time division control module in a time division control manner; the processing module 140 is configured to According to the control signal sequence, the collected near-infrared fluorescence image and the visible light image are subjected to image segmentation, feature extraction, image registration, etc., to realize fusion of the visible light image and the fluorescence image, and output the fused image; and according to the
  • the multi-spectral light source module 110 the optical signal acquisition module 120, the time division control module 130, and the processing module 140 will be described in detail.
  • the multi-spectral light source module 110 may include a background light source 111, a first multi-spectral switcher 112, and a near-infrared laser 113.
  • the background light source 111 is for providing visible light.
  • the near-infrared light source 113 is used to provide near-infrared light, and can be set as an LED lamp having a center wavelength of 760 nm.
  • the first multi-spectral switcher 112 controls the background light source 111 and the near-infrared light source 113 to be alternately turned on and off according to the time division control signal sequence from the time division control module 130, thereby illuminating the visible light when the optical signal acquisition module 120 collects the fluorescent image, and when the optical The signal acquisition module 120 illuminates near-infrared light when acquiring a visible light background image.
  • the front end of the near-infrared light source 113 can be placed with a near-infrared filter having a wavelength of 707 nm to 780 nm.
  • the front end of the background light source 111 may be placed with a visible light filter having a wavelength of 400 nm to 650 nm.
  • the first multispectral switcher 112 switches to filter position 1, which places the bandpass filter wavelength at 707 nm - 780 nm.
  • the first multispectral switcher 112 switches to the position filter 2, where no filter is placed.
  • the wavelength of visible light irradiated by the background light source 111 can be further optimized by placing a band pass filter having a wavelength of 400 nm to 650 nm at the filter position 2.
  • the optical signal acquisition module 120 can include a camera 121, a second multi-spectral switcher 122, and a timing signal controller 123.
  • the camera 121 is used to acquire near-infrared fluorescence images and visible light images. Most industrial grade cameras are suitable for visible light images.
  • the camera's relevant parameters can be set to: quantum efficiency should be higher than 30% at 800 nm, frame rate is greater than 30 fps, and image source size is greater than 5 microns.
  • the timing signal controller 123 is configured to receive the time division control signal sequence from the time division control module 130, and control the second multispectral switcher 122 to switch between the position 1' and the position 2' according to the received time division control signal sequence, so that The camera performs the acquisition of the corresponding visible light image and fluorescent image.
  • the second multi-spectral switcher 122 is disposed in front of the camera 121 End for switching according to a sequence of delay control signals from the timing signal controller.
  • the second multi-spectral switcher 122 switches to position 1', and the wavelength at which the filter is placed at position 1' is 808-880 nm.
  • the second multi-spectral switcher 122 switches to position 2', which has no filter at position 2'.
  • the time division control module 130 includes a timing signal generator 131 and a signal controller 132.
  • the timing signal generator 131 generates a control signal according to different signal sources and transmits the generated control signal to the signal controller 132.
  • the signal controller 132 converts the control signal from the timing signal generator 131 into a control signal sequence having a system usable format and transmits it to the first spectral switch 112 and the timing signal controller 123.
  • the timing signal controller 123 appropriately delays the received sequence of control signals and uses the delayed sequence of control signals to control the operation of the second spectral switcher 122.
  • the timing signal controller 123 can be omitted, and the control signal sequence and the delayed control signal sequence are directly generated by the signal controller 132 to control the operations of the first spectral switch 112 and the second spectral switch 122, respectively.
  • the processing module 140 includes a timing control feedback module 141 and an image processing module 142.
  • the timing control feedback module 141 monitors the control signal sequence output by the time division control module 130 based on the visible light image and the fluorescence image acquired by the camera 121. Specifically, the timing control feedback module 141 receives the visible light image and the fluorescence image acquired by the camera 121, and determines whether the first multi-spectral switch 112 and/or the second need to be adjusted according to the received light intensity of the visible light image and the fluorescent image.
  • the operation of the multispectral switcher 122 and in the event that it is determined that adjustments to the operation of the first multispectral switcher 112 and/or the second multispectral switcher 122 are required, a feedback signal is returned to the signal controller 132.
  • the signal controller 132 adjusts the sequence of control signals to be transmitted to the respective first multispectral switcher 112 and/or second multispectral switcher 122 based on the received feedback signal.
  • the timing control feedback module 141 determines that the brightness of the received visible light image is too large, a feedback signal is returned to the signal controller 132, indicating that the turn-on time of the background light source 111 is shortened or the turn-on time of the near-infrared light source 113 is increased, or the camera is shortened.
  • 121 collecting the duration of the visible light image; when the timing control feedback module 141 determines that the brightness of the received visible light image is too small, returning a feedback signal to the signal controller 132, indicating increasing the turn-on time of the background light source 111 or shortening the near-infrared light source 113 The on time, or the duration of the extended camera 121 to capture the visible light image.
  • the timing control feedback module 141 can also provide a signal controller according to the received brightness image and the brightness (light intensity parameter) of the fluorescent image.
  • 132 returns a feedback signal indicating a change in the grating in the first multispectral switch 1 and/or the second multispectral switch 2 to change the respective light illumination intensity and/or the acquisition time of the corresponding image.
  • the first multi-spectral switcher 112 and the second multi-spectral switcher 122 may also be employed as long as the first plurality of image light intensities can be adjusted according to the received visible light image and the fluorescence image. The operation of the spectral switcher 112 and/or the second multispectral switcher 122 is sufficient.
  • the timing control feedback module 141 can also receive a sequence of control signals from the signal controller 132, first and second feedback control signal sequences from the first multispectral switch 112 and the second multispectral switch 122, respectively, and The control signal sequence is compared to the first and second feedback control signal sequences, respectively. For example, the timing control feedback module 141 can compare the respective start and end points of the respective control signal sequences. If the timing offset exceeds the first predetermined threshold but is less than the second predetermined threshold, the timing control feedback module 141 feeds back information to the signal controller 132 to adjust the output control signal sequence.
  • the timing control feedback module 141 determines that the error cannot be automatically adjusted, a report error is generated, an error report is sent to the signal controller 132, the control component stops the acquisition, and the timing is synchronized and then the timing is started. run.
  • the image processing module 142 is configured to process the acquired visible light image and fluorescent image at intervals of each time sequence.
  • the specific processing may include segmentation, feature extraction, and pseudo color conversion of the collected near-infrared fluorescence image; brightness adjustment and optimization of the collected visible light image, and fusion of the processed visible light image with the processed near-infrared fluorescence image And output the fused image.
  • FIG. 3 is a schematic diagram showing the control timing of the time division control module of FIG.
  • the first multi-spectral switcher 112 according to the control signal sequence from the signal controller 132, at time t1, the background light source 111 is turned off and the near-infrared light source 113 is turned on to illuminate the subject with the fluorescent signal.
  • the first multi-spectral switcher 112 switches to the filter position 1, where a band pass filter having a wavelength of 707 nm to 780 nm is placed.
  • the timing signal controller 123 in the optical signal acquisition module 120 receives the control signal sequence from the signal controller 132, performs a corresponding delay, and controls the second multi-spectral switch 122 so that when the reflected fluorescent signal reflected from the object is reached, The second multi-spectral switcher 122 is switched to the position 1', and the wavelength at which the filter is placed at the position 1' is 808 nm to 880 nm, thereby obtaining a fluorescence image of the subject, and outputting to the processing module 140.
  • the background light source 111 is turned on and the near-infrared light source 113 is turned off to illuminate the subject with a visible fluorescent signal.
  • the first multi-spectral switcher 112 switches to the filter position 2, which has no filter, or is provided with a visible light filter having a wavelength of 400 nm to 650 nm.
  • the timing signal controller 123 in the optical signal acquisition module 120 controls the second multi-spectral switcher 122 according to the timing so that when the reflected visible light signal reflected from the object to be detected arrives, the second multi-spectral switcher 122 switches to the position 2', There is no filter at this position, thereby obtaining a visible light image of the subject, and outputting it to the processing module 140.
  • the specific process for image processing and excitation fluorescence imaging involves two interrelated processes: the excitation process and the emission process.
  • the excitation process uses a single or narrow-band excitation source to illuminate a particular imaging area, and the excitation light enters the interior through the surface and forms a certain intensity distribution within it.
  • the emission process means that the internal fluorophore absorbs the energy of the external excitation light and converts it into a longer-wavelength, lower-energy emission light, which emits light, can be filtered by a specific wavelength filter and is highly sensitive. Combine to get.
  • the two processes of excitation and emission can be described by the coupling of two diffusion equations:
  • ⁇ represents the three-dimensional space of the imaged object
  • subscripts x and m represent excitation and emission light, respectively
  • ⁇ x and ⁇ m represent photon density
  • ⁇ ax and ⁇ am represent optical absorption coefficients
  • ⁇ sx and ⁇ sm represent optical scattering coefficients
  • g represents an anisotropy coefficient.
  • n the refractive index of the biological tissue, n ⁇ 1.4 for a non-contact excitation fluorescence tomography system (imaging object in air).
  • the light source distribution is obtained until the number of support set elements exceeds a certain threshold or the residual is less than the threshold.

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Abstract

一种手持式分子影像导航系统，包括多光谱光源模块，用于根据控制信号序列，以时分控制方式提供多个不同谱段的光，以便照射受检对象；时分控制模块，用于产生所述控制信号序列；光学信号采集模块，用于根据所述时分控制模块提供的控制信号序列，以时分控制方式采集受检对象的近红外荧光图像和可见光图像；处理模块，用于根据所述控制信号序列对采集的近红外荧光图像和可见光图像进行图像处理，实现可见光图像与荧光图像的融合并输出融合图像，以及根据采集的近红外荧光图像和可见光图像输出反馈信号，以便对所述控制信号序列进行优化。

Description

一种手持式分子影像导航系统 技术领域
本发明涉及一种成像系统，特别是一种手持式分子影像导航系统。
背景技术
作为无创可视化成像技术的新方法和手段，分子影像在本质上反映了分子调控的改变所引发的生物体生理分子水平变化和整体机能的变化。因此，在分子水平上在体(in vivo)研究基因、生物大分子和细胞的生命活动是一种重要技术，其中基于分子技术、断层成像技术、光学成像技术、模拟方法学的在体生物光学成像技术的基础研究，已经成为分子影像领域研究的热点和难点之一。
分子影像设备将传统医学影像技术与现代分子生物学相结合，能够从细胞、分子层面观测生理或病理变化，具有无创伤、实时、活体、高特异性、高灵敏度以及高分辨率显像等优点。利用分子影像技术，一方面可加快药物的研制开发速度，缩短药物临床前研究时间；提供更准确的诊断，使治疗方案最佳地匹配病人的基因图谱。另一方面，可以在生物医学领域进行应用，实现在体的定量分析、影像导航、分子分型等目标。然而，利用这种方法的系统相对复杂，操作简易性及使用舒适性方面有待进一步提高。
因此本发明提出了一种手持式分子影像导航系统，通过分时控制方法不同光谱的荧光及可见光的实时成像，增强应用的适用范围。
发明内容
本发明实施例提供了一种手持式分子影像导航系统，包括：
多光谱光源模块，用于根据控制信号序列，以时分控制方式提供多个不同谱段的光，以便照射受检对象；
时分控制模块，用于产生所述控制信号序列；
光学信号采集模块，用于根据所述时分控制模块提供的控制信号序列，以时分控制方式采集受检对象的近红外荧光图像和可见光图像；
处理模块，用于根据所述控制信号序列对采集的近红外荧光图像和可见光图 像进行图像处理，实现可见光图像与荧光图像的融合并输出融合图像，以及根据采集的近红外荧光图像和可见光图像输出反馈信号，以便对所述控制信号序列进行优化。
优选地，手持式分子影像系统还包括手持式系统容纳模块，用于容纳所述多光谱光源模块、所述时分控制模块和所述信号采集模块。
优选地，所述多光谱光源模块包括：
背景光源，用于提供可见光；
近红外光源，用于提供近红外光；以及
第一多光谱切换器，用于根据来自所述时分控制模块的时分控制信号序列，控制背景光源和近红外光源交替开启和关闭，从而当光学信号采集模块采集荧光图像时照射可见光，以及当采集可见光背景图像时照射近红外光。
优选地，所述光学信号采集模块包括：
相机，用于采集受检对象的近红外荧光图像及可见光图像；
第二多光谱切换器，设置于相机的前端；
时序信号控制器，用于接收来自时分控制模块的控制信号序列，并根据接收到的控制信号序列控制第二多光谱切换器的切换，以便相机进行相应可见光图像和荧光图像的采集。
优选地，所述时分控制模块包括：
时序信号发生器，用于根据不同的光信号源产生控制信号；以及
信号控制器，用于将来自时序信号发生器的控制信号转换成具有系统可用格式的控制信号序列，以控制第一光谱切换器和第二光谱切换器的操作。
优选地，所述处理模块包括：
时序控制反馈模块，用于根据采集的可见光图像和荧光图像来监控所述时分控制模块输出的控制信号序列，确定是否需要调整第一多光谱切换器和/或第二多光谱切换器的操作，并基于确定结果向信号控制器返回反馈信号；
图像处理模块，用于在每个时序的间隔中对采集到的可见光图像和荧光图像进行图像处理，对处理后的可见光图像与处理后的近红外荧光图像进行融合，并输出融合图像。
本发明的实施例至少具有以下技术效果：
首先，由于采用手持式设备采集图像，在生物医学应用的过程中可以简化操作，拓展应用范围。
其次，由于采用分时控制的方法，使得图像的采集以及处理实现了多光谱实时成像。此外，通过设置多光谱切换器以及时分控制模块，将多光谱光源模块切换与时序控制配合使用，使得能够有效实现分子影像导航，探测光强达到最大，有效保留有用信息。在实际操作中不仅可以看到较强的荧光信息，也可以使得观测人员看到可见光的信息，两个光谱的光线并不会相互影响。
附图说明
图1示出了根据本发明实施例的手持式系统容纳模块的外观示意图；
图2示出了根据本发明实施例的手持式分子影像导航系统的方框图；
图3示出了图2中的时分控制模块的控制时序示意图。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚明白，以下结合具体实施例，并参照附图，对本发明进一步详细说明。
本发明实施例基于分子影像中的激发荧光成像，提供了一种手持式分子影像导航系统。
图1是根据本发明实施例的手持式系统容纳模块的外观示意图。图2是根据本发明实施例的手持式分子影像导航系统的方框图。如图2所示，该手持式分子影像导航系统可以包括多光谱光源模块110，用于以时分控制方式提供多个不同谱段的光，以便照射受检对象；时分控制模块130，用于产生控制信号序列；光学信号采集模块120，用于根据所述时分控制模块提供的控制信号序列，以时分控制方式采集受检对象的近红外荧光图像和可见光图像；处理模块140，用于根 据所述控制信号序列对采集的近红外荧光图像和可见光图像进行图像分割、特征提取、图像配准等处理，实现可见光图像与荧光图像的融合并输出融合图像；以及根据采集的近红外荧光图像和可见光图像输出反馈信号，以便对控制信号序列进行优化。手持式分子影像系统还包括图1所示的手持式系统容纳模块，用于容纳所述多光谱光源模块、所述时分控制模块和所述信号采集模块，以便于进行操作并保证成像的有效进行。
接下来将分别详细描述多光谱光源模块110、光学信号采集模块120、时分控制模块130和处理模块140的操作。
多光谱光源模块110可以包括背景光源111、第一多光谱切换器112和近红外激光器113。背景光源111用于提供可见光。近红外光源113用于提供近红外光，并且可以设置为中心波长是760nm的LED灯。第一多光谱切换器112根据来自时分控制模块130的时分控制信号序列，控制背景光源111和近红外光源113交替开启和关闭，从而当光学信号采集模块120采集荧光图像时照射可见光，以及当光学信号采集模块120采集可见光背景图像时照射近红外光。近红外光源113的前端可以放置近红外滤光片，波长为707nm-780nm。背景光源111的前端可以放置可见光滤光片，波长为400nm-650nm。优选地，当照射荧光序列信号时，第一多光谱切换器112切换至滤光片位置1，该位置放置带通滤光片波长为707nm-780nm。当照射可见光序列信号时，第一多光谱切换器112切换至位置滤光片2，该位置不放置滤光片。利用在滤光片位置2放置波长为400nm-650nm的带通滤光片，可以进一步优化背景光源111照射的可见光的波长。
光学信号采集模块120可以包括相机121、第二多光谱切换器122和时序信号控制器123。相机121用于采集近红外荧光图像及可见光图像。对于可见光图像大部分工业级相机均适用。可以将相机的相关参数设置为：量子效率在800nm处应高于30％，帧速大于30fps，像源尺寸大于5微米。时序信号控制器123用于接收来自时分控制模块130的时分控制信号序列，并根据接收到的时分控制信号序列控制第二多光谱切换器122在位置1’和位置2’之间进行切换，以便相机进行相应可见光图像和荧光图像的采集。第二多光谱切换器122设置于相机121的前 端，用于根据来自时序信号控制器的延迟控制信号序列进行切换。当荧光图像信号到达时，第二多光谱切换器122切换至位置1’，位置1’处放置滤光片的波长为808-880nm。当可见光图像信号达到时，第二多光谱切换器122切换至位置2’，位置2’处无滤光片。
时分控制模块130包括时序信号发生器131及信号控制器132。时序信号发生器131根据不同的信号源产生控制信号，并将产生的控制信号发送给信号控制器132。信号控制器132将来自时序信号发生器131的控制信号转换成具有系统可用格式的控制信号序列，并发送到第一光谱切换器112和时序信号控制器123。时序信号控制器123将接收到的控制信号序列进行适当延迟，并使用延迟的控制信号序列来控制第二光谱切换器122的操作。当然，可以省略时序信号控制器123，由信号控制器132直接产生控制信号序列和经延迟的控制信号序列，来分别控制第一光谱切换器112和第二光谱切换器122的操作。
处理模块140包括时序控制反馈模块141和图像处理模块142。时序控制反馈模块141根据由相机121采集的可见光图像和荧光图像来监控时分控制模块130输出的控制信号序列。具体地，时序控制反馈模块141接收由相机121采集的可见光图像和荧光图像，根据接收到的可见光图像和荧光图像的图像光强度来确定是否需要调整第一多光谱切换器112和/或第二多光谱切换器122的操作，并在确定需要对第一多光谱切换器112和/或第二多光谱切换器122的操作进行调整的情况下，向信号控制器132返回反馈信号。信号控制器132根据接收到的反馈信号来调整要发送到相应第一多光谱切换器112和/或第二多光谱切换器122的控制信号序列。
例如时序控制反馈模块141确定接收到的可见光图像的亮度过大，则向信号控制器132返回反馈信号，指示缩短背景光源111的开启时间或增大近红外光源113的开启时间，或指示缩短相机121采集可见光图像的持续时间；当时序控制反馈模块141确定接收到的可见光图像的亮度过小时，则向信号控制器132返回反馈信号，指示增大背景光源111的开启时间或缩短近红外光源113的开启时间，或指示延长相机121采集可见光图像的持续时间。此外，根据接收到的可见光图像和荧光图像的亮度(光强度参数)，时序控制反馈模块141还可以向信号控制器 132返回反馈信号，指示改变第一多光谱切换器1和/或第二多光谱切换器2中的光栅，来改变相应光照射强度和/或相应图像的采集时间。本领域技术人员可以理解，还可以采用第一多光谱切换器112和第二多光谱切换器122的其他操作组合，只要能够根据接收到的可见光图像和荧光图像的图像光强度来调整第一多光谱切换器112和/或第二多光谱切换器122的操作即可。
此外，时序控制反馈模块141还可以接收来自信号控制器132的控制信号序列、分别来自第一多光谱切换器112和第二多光谱切换器122的第一和第二反馈控制信号序列，并将控制信号序列与第一和第二反馈控制信号序列分别进行比较。例如时序控制反馈模块141可以将各个控制信号序列的相应开始及结束点进行比较。如果时序偏差超过第一预定阈值但小于第二预定阈值，则时序控制反馈模块141向信号控制器132反馈信息，以便调整输出的控制信号序列。如果时序偏差超过第二预定阈值，时序控制反馈模块141确定无法自动对误差进行调整，则产生报告错误，将错误报告发送至信号控制器132，以控制部件停止采集，并时序同步后再启动时序运行。
图像处理模块142配置为在每个时序的间隔中对采集到的可见光图像和荧光图像进行处理。具体处理过程可以包括对采集到近红外荧光图像进行分割、特征提取以及伪彩色变换；对采集到的可见光图像进行亮度调整及优化，将处理后的可见光图像与处理后的近红外荧光图像进行融合，并输出融合图像。
接下来，将结合图2和图3来详细描述根据本发明实施例的分子影像导航系统的控制时序。
图3示出了图2中时分控制模块的控制时序示意图。如图3所示，第一多光谱切换器112根据来自信号控制器132的控制信号序列，在时刻t1，背景光源111关闭且近红外光源113开启以向受检对象照射荧光信号。此时，第一多光谱切换器112切换至滤光片位置1，该位置放置波长为707nm-780nm的带通滤光片。光学信号采集模块120中的时序信号控制器123接收来自信号控制器132的控制信号序列，进行相应延迟，控制第二多光谱切换器122，以便当从受检对象反射的反射荧光信号到达时，第二多光谱切换器122切换至位置1’，位置1’处放置滤光片的波长为808nm-880nm，从而得到受检对象的荧光图像，并输出到处理模块140。
在时刻t2，背景光源111开启且近红外光源113关闭，以向受检对象照射可见荧光信号。此时，第一多光谱切换器112切换至滤光片位置2，该位置无滤光片，或设置有波长为400nm-650nm的可见光滤光片。光学信号采集模块120中的时序信号控制器123根据时序控制第二多光谱切换器122，以便当从受检对象反射的反射可见光信号到达时，第二多光谱切换器122切换至位置2’，该位置无滤光片，从而得到受检对象的可见光图像，并输出到处理模块140。
对于图像处理与激发荧光成像的具体过程，包含两个相互关联的过程：激发过程和发射过程。激发过程是使用单色或窄带的激发光源照射特定的成像区域，激发光通过表面进入内部，并在其内部形成一定的光强分布。发射过程是指内部的荧光团会吸收外来激发光的能量，并将其部分转化为波长更长、能量更低的发射光，发射光透出，可由特定波长的滤光片和高灵敏度的探测器组合来获取。激发和发射两个过程可以通过两个扩散方程的耦合来进行描述：
Figure PCTCN2014089150-appb-000001
Figure PCTCN2014089150-appb-000002
其中，Ω代表成像对象的三维空间，下标x和m分别表示激发和发射光；Φx和Φm表示光子密度；μax和μam表示光学吸收系数，μsx和μsm表示光学散射系数，Dx，m＝(3μax，am+3μsx，sm(1-g))-1表示扩散系数，g表示表示各向异性系数。
利用扩散方程对激发荧光断层成像问题建模时将加入Robin边界条件：
Figure PCTCN2014089150-appb-000003
其中，
Figure PCTCN2014089150-appb-000004
表示成像对象表面边界，表示表面边界上指向外的单位法向量，v表征边界内和边界外光学折射系数的偏差。v＝(1-R)/(1+R)，其中参数R由以下公式得出：
R≈-1.4399n-2+0.7099n-1+0.6681+0.0636n    (6)
n表示生物组织折射率，对非接触式的激发荧光断层成像系统(成像对象在空气中)而言，n≈1.4。
式子(3)和(4)经过有限元离散后，可以得到如下的矩阵形式方程：
KxΦx＝Qx    (7)
KmΦm＝FX    (8)
由于激发过程外部激发光强分布可以由(7)直接求解得出，故方程可简化为：
Figure PCTCN2014089150-appb-000005
通过计算(9)求出其最小二乘解：
Figure PCTCN2014089150-appb-000006
通过上述计算，直到支撑集元素的数量超过一定阀值或残差小于阀值为止，得到光源分布。
以上所述的具体实施例，对本发明的目的、技术方案和有益效果进行了进一步详细说明，所应理解的是，以上所述仅为本发明的具体实施例而已，并不用于限制本发明，凡在本发明的精神和原则之内，所做的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。

Claims (6)

  1. 一种手持式分子影像导航系统，包括：
    多光谱光源模块(110)，用于根据控制信号序列，以时分控制方式提供多个不同谱段的光，以便照射受检对象；
    时分控制模块(130)，用于产生所述控制信号序列；
    光学信号采集模块(120)，用于根据所述时分控制模块提供的控制信号序列，以时分控制方式采集受检对象的近红外荧光图像和可见光图像；
    处理模块(140)，用于根据所述控制信号序列对采集的近红外荧光图像和可见光图像进行图像处理，实现可见光图像与荧光图像的融合并输出融合图像，以及根据采集的近红外荧光图像和可见光图像输出反馈信号，以便对所述控制信号序列进行优化。
  2. 根据权利要求1所述的手持式分子影像系统，还包括手持式系统容纳模块用于容纳所述多光谱光源模块、所述时分控制模块和所述信号采集模块。
  3. 根据权利要求1所述的手持式分子影像系统，其中，所述多光谱光源模块包括：
    背景光源，用于提供可见光；
    近红外光源，用于提供近红外光；以及
    第一多光谱切换器，用于根据来自所述时分控制模块的时分控制信号序列，控制背景光源和近红外光源交替开启和关闭，从而当光学信号采集模块采集荧光图像时照射可见光，以及当采集可见光背景图像时照射近红外光。
  4. 根据权利要求1所述的手持式分子影像系统，其中，所述光学信号采集模块包括：
    相机，用于采集受检对象的近红外荧光图像及可见光图像；
    第二多光谱切换器，设置于相机的前端；
    时序信号控制器，用于接收来自时分控制模块的控制信号序列，并根据接收 到的控制信号序列控制第二多光谱切换器的切换，以便相机进行相应可见光图像和荧光图像的采集。
  5. 根据权利要求4所述的手持式分子影像系统，其中，所述时分控制模块包括：
    时序信号发生器，用于根据不同的信号源产生控制信号；以及
    信号控制器，用于将来自时序信号发生器的控制信号转换成具有系统可用格式的控制信号序列，以控制第一光谱切换器和第二光谱切换器的操作。
  6. 根据权利要求5所述的手持式分子影像系统，其中，所述处理模块包括：
    时序控制反馈模块，用于根据采集的可见光图像和荧光图像来监控所述时分控制模块输出的控制信号序列，确定是否需要调整第一多光谱切换器和/或第二多光谱切换器的操作，并基于确定结果向信号控制器返回反馈信号；
    图像处理模块，用于在每个时序的间隔中对采集到的可见光图像和荧光图像进行图像处理，对处理后的可见光图像与处理后的近红外荧光图像进行融合，并输出融合图像。
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